New Studies in Molecular Recognition: Synthetic "hosts" that bind particular "guests" have tremendous potential to benefit human health. Promising applications include drug delivery systems/membrane transport, the detection and separation of pollutants, and medical diagnostics. The proposed research studies a new class of synthetic hosts-"molecular tweezers"-that efficiently bind nitro--polycyclic aromatic hydrocarbons (nitro-PAH) and nucleotide bases. Nitro-PAH are pervasive pollutants, produced in almost all combustion processes. They pose a serious human health concern because they are potent mutagens and some have been shown to be carcinogenic. The proposed research seeks to develop new molecular tweezers with enhanced affinity for nitrated pyrenes, a group of nitro-PAH that account for the bulk of mutagenicity in environmental samples. These molecular tweezers will be covalently connected to silica gel creating a new chemically bonded stationary phase (CBSP) that will be packed into high pressure liquid chromatography (HPLC) columns. In turn, analytical methods for isolating and detecting nitro-PAH will be developed using these HPLC co mns. The general and efficacious use of synthetic hosts in other applications requires both a deeper understanding of current host-guest systems and the development of new hosts with novel properties. Thus, a general objective of the proposed research is to develop strategies for understanding weak noncovalent forces and for designing hosts that exhibit the properties required in these applications. These studies will also use "molecular tweezers." Since this class of hosts uses binding forces common to all noncovalent interactions, the results of these studies may be applicable to other host-guest systems. One investigation will establish whether HPLC retention times on CBSPs can be used to determine the corresponding complexation parameters (i.e. deltaGo, deltaHo, deltaSo) in solution. If so, this may provide a general complexation assay that is both rapid and accurate. A second study will determine whether multiparameter approaches can be applied to solvation effects on complexation parameters. If so, this may provide a general method for factoring host-guest complex stabilities, and for understanding the origin of binding efficiencies. Several molecular tweezers with novel properties will be studied. Additional contacts will be built into a design criteria for extremely tight guest binding by synthetic hosts. Additionally, this system will test the Page and Jencks "anchor principle" that suggests these additional binding contacts will contribute their full enthalpic worth to deltaGo. A second molecular tweezer has been designed to bind adenine very "tightly", but with a moderate affinity. This strategy, which is similar to that used by enzymes in maintaining a moderate Km, may find application in transport or catalysis.